The interplay between microRNAs and the neurotrophin receptor tropomyosin-related kinase C controls proliferation of human neuroblastoma cells
The interplay between microRNAs and the neurotrophin receptor tropomyosin-related kinase C controls proliferation of human neuroblastoma cells
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DOI：
10.1073/pnas.0700071104
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发表时间：
2007-05-08
影响因子：
11.1
通讯作者：
Caffarelli, Elisa
中科院分区：
文献类型：
--
作者：
Laneve, Pietro;Di Marcotullio, Lucia;Caffarelli, Elisa
微小RNA（miRNAs）是一类微小的非编码RNA，其作为基因表达调节剂的功能对于细胞生长和分化的恰当调控至关重要。尽管许多不同细胞系统的miRNA表达谱已被确定，但对它们所涉及的调控网络的阐释才刚刚起步。在这项工作中，我们确定了三种神经元miRNAs（9、125a和125b）在控制人神经母细胞瘤细胞增殖中具有关键作用。我们表明这些分子通过抑制一个共同靶点，即神经营养因子受体原肌球蛋白相关激酶C的截短异构体，以累加的方式发挥作用，并且我们证明该异构体的下调对于调节神经母细胞瘤细胞生长至关重要。与它们的功能一致，这些miRNAs在原发性神经母细胞瘤肿瘤中被发现是下调的。
MicroRNAs (miRNAs) are tiny noncoding RNAs whose function as modulators of gene expression is crucial for the proper control of cell growth and differentiation. Although the profile of miRNA expression has been defined for many different cellular systems, the elucidation of the regulatory networks in which they are involved is only just emerging. In this work, we identify a crucial role for three neuronal miRNAs (9, 125a, and 125b) in controlling human neuroblastoma cell proliferation. We show that these molecules act in an additive manner by repressing a common target, the truncated isoform of the neurotrophin receptor tropomyosin-related kinase C, and we demonstrate that the down-regulation of this isoform is critical for regulating neuroblastoma cell growth. Consistently with their function, these miRNAs were found to be down-modulated in primary neuroblastoma tumors.